Both the virginiamycin and elfamycin families of antibiotics represent rather small and homogeneous groups of chemical agents which display interesting biological activity. The compounds are produced by fermentation of microorganisms of the streptomyces or actinoplanes species. All of the antibiotics of the virginiamycin family can be assigned to either one of the two basic primary structures known as A and B. An extensive review of the structure and mechanisms of action of the virginiamycin antibiotics is presented by Cocito in Microbiological Reviews, 43, pp 145-198 (1979). Certain of the elfamycins are discussed by Maehr et al., in Journal of Antibiotics, 361 (1979).
While the virginiamycins and elfamycins have been employed primarily in the treatment of bacterial infections, they also have found utility in the promotion of growth in domestic animals. As pointed out by Lucas in Proc. Nutr. Soc. (1972), 31, pp 1-8, virginiamycins are employed as growth stimulants for both poultry and swine. Virginiamycins also have been used in the form of feed additives to effect growth promotion in ruminants such as sheep and cattle. Maehr, in U.S. Pat. No. 4,218,560, describes the use of certain elfamycins as growth promotants in farm animals, including cattle.
Cocito reports that the virginiamycin compounds are effective in promoting growth in animals by the inhibition of the intestinal flora, particularly of gram-positive bacteria which interfere with the absorption of nutrients. While the precise mode of action is not known, it is established that this class of antibiotics is effective in promoting nutrient absorption and growth rate of several farm animals. Their commercial use as growth promoters is particularly favorable since they display extremely low toxicity, there is a lack of accumulation in animal tissues, there is practically an undetectable production of resistant mutants in the intestinal flora, and they are biodegradable in animal feces.
While the virginiamycins and elfamycins have been employed in the growth stimulation of ruminants which are grown for meat production for human consumption, the antibiotics heretofore have not been employed in lactating ruminants. It has now been found that when administered to lactating ruminants, the compounds do not promote growth of the animal, but instead cause an improvement in the milk which is produced. A typical improvement effected in increased production without an adverse affect on milk fat or protein content.
This nutritive response is particularly surprising in view of the mechanism of feed utilization by ruminant animals. Carbohydrates, which are the primary nutritive portion of ruminant feed, is degraded in the rumen to pyruvate, which in turn is metabolized to acetate, propionate and butyrate. The latter are collectively known as volatile fatty acids (VFA's).
The VFAs are absorbed from the gut and employed for energy production and growth. It is known that propionate is much more efficiently utilized than either acetate or butyrate. Some of the agents which are known to increase feed utilization efficiency accordingly operate by altering the ruminant fermentation process so that propionate production is increased at the expense of acetate and butyrate. Agents which cause an increase in propionate with a concomitant decrease in acetate cause ruminants growth for meat production to gain more weight without consuming more feed, or to maintain a normal weight pattern while consuming less feed. Such agents are therefore very beneficial to the beef industry.
The requirements and objectives of feed utilization of lactating ruminants such as dairy cows differ considerably from those of ruminants raised for meat production. Ruminal VFA production is of course of primary importance, since it relates directly to the normal maintenance of the animal, as well as to the quality and quantity of the milk produced by the animal. In the lactating ruminant, however, energy for lactation is the most limiting factor in milk production. Acetate is required for milk fat synthesis, while propionate is utilized to produce glucose, which in turn is required for lactose synthesis, and also has a minor role in milk fat production. Butyrate is more glycogenic than lipogenic, the lipogenic aspect being indirect since butyrate must first be degraded to acetate units before it can be utilized for long chain fatty acid synthesis, i.e., milk fat.
Accordingly, in order to increase milk production in lactating ruminants, it is necessary to alter ruminant fermentation (ie. VFA production), but not at a dramatic expense of either acetate or butyrate production. Significantly reduced acetate and butyrate levels result in drastically reduced milk fat content, thereby rendering milk production less efficient with respect to both quality and economically (bulk milk prices are determined in part by milk fat content).
It has now been discovered that the elfamycin and virginiamycin families of antibiotics are effective in improving milk production in lactating ruminants without causing an adverse affect upon milk quality. Such improvement has been mainifested in the form of increased milk volume without a decrease in fat content. The fact that this improvement can be realized is particularly surprising in view of the report by Parkhurst and McGowan in the 1978 Ellinbank Dairy Research Institute Report from Australia. These authors administered varying doses of monensin to dairy cows. Monensin is a polyether antibiotic widely employed as an enhancer of ruminant feed utilization efficiency. The authors concluded that, at all administration rates evaluated, fat-corrected-milk production was no different from that of non-treated control animals.